A research report from Orient Securities Company Limited indicates that autologous CAR-T therapy possesses significant appeal due to its excellent efficacy, with global sales approaching $6 billion in 2025. Recent positive data from T-cell engagers (TCEs) have raised market concerns about the prospects of autologous CAR-T. The primary reasons are the complex manufacturing and administration processes and the prominent cost-related price disadvantages of autologous CAR-T, especially when therapeutic outcomes are comparable. In vivo CAR-T is identified as a highly promising direction to address these challenges. Currently, this field is largely in the early clinical stages, but preliminary data have already validated its efficacy. Its safety profile is expected to potentially surpass that of autologous CAR-T. Multinational corporations (MNCs) have already entered the space, forming numerous significant partnerships or acquisitions. A substantial number of domestic companies are also making布局, with multiple future transactions anticipated. The main viewpoints from Orient Securities Company Limited are as follows:

The emergence of TCEs has highlighted the challenges facing autologous CAR-T. CAR-T therapy is synonymous with top-tier efficacy in hematologic malignancies and the potential for a "curative" single administration. Globally, 15 autologous CAR-T products have been approved, achieving sales of $5.9 billion in 2025, a 30% year-on-year increase. Data from the MajesTEC-3 study presented at ASH 2025, investigating the BCMA-targeted TCE teclistamab in combination with daratumumab for relapsed/refractory multiple myeloma, showed efficacy not inferior to CARVYKTI, with even superior progression-free survival rates and a favorable safety profile. This contrast underscores the disadvantages of autologous CAR-T, including its complex production, logistical challenges, high cost, and pricing, necessitating new breakthroughs.

In vivo CAR-T demonstrates considerable potential, with preliminary data providing validation. CAR-T therapies aiming for simpler production, easier administration, and lower costs primarily fall into two categories: allogeneic CAR-T and in vivo CAR-T. Considering that allogeneic approaches still require ex vivo T-cell modification and lymphodepletion, coupled with the risk of fatal graft-versus-host disease (GvHD), the report suggests in vivo CAR-T may hold greater promise. Currently, there are over 20 in vivo CAR-T pipelines in clinical development, most at early stages. Human data has been disclosed for five in vivo CAR-T products. Lentiviral vector-based products have demonstrated confirmed short-term efficacy in hematologic cancers, comparable to autologous CAR-T, with some showing potentially better safety; long-term efficacy durability and safety post-administration require further monitoring. LNP-based products, while requiring multiple doses, exhibit excellent safety and have shown preliminary efficacy signals in autoimmune diseases, suggesting potential for significant future performance in the autoimmune领域.

MNCs are actively pursuing布局, enhancing certainty. Since 2025, over 10 transactions related to in vivo CAR-T have occurred, with MNCs like AstraZeneca, AbbVie, and Bristol Myers Squibb actively entering the field through major collaborations or acquisitions, predominantly involving lentiviral-based pipelines or companies. Regarding data catalysts, more than ten new clinical readouts are expected this year, mostly first-time data disclosures for various pipelines, with previously disclosed early-data pipelines likely reporting updated results. The report concludes that the clinical performance of in vivo CAR-T has received initial validation, and the certainty of the technological pathway continues to increase. It is poised to potentially become a mainstream form of CAR-T therapy in the future. Demand from MNCs is robust. Although domestic companies' progress slightly lags, they lead in the number of布局, and multiple future transactions are anticipated.

Risk factors include the potential for innovative drug研发 failure, intensifying market competition, and risks associated with the commercialization of innovative drugs.